What is the best oral antibiotic for an adult patient with cellulitis on the arm, without any underlying medical conditions or allergies?

Best Oral Antibiotic for Arm Cellulitis

For an adult with uncomplicated cellulitis on the arm, cephalexin 500 mg orally every 6 hours for 5 days is the best first-line choice, providing excellent coverage against the primary pathogens (beta-hemolytic streptococci and methicillin-sensitive Staphylococcus aureus) with a 96% success rate. 1

First-Line Treatment Algorithm

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis. 1 The Infectious Diseases Society of America provides A-I level evidence supporting this approach, as MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings. 1

Recommended Oral Agents (in order of preference):

• Cephalexin 500 mg orally every 6 hours - preferred first-line agent 1, 2
• Dicloxacillin 250-500 mg every 6 hours - equally effective alternative 1, 2
• Amoxicillin-clavulanate 875/125 mg twice daily - provides single-agent coverage for both streptococci and common skin flora 1
• Penicillin V 250-500 mg four times daily - appropriate for typical cellulitis 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1 High-quality randomized controlled trial evidence demonstrates that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1, 3 A landmark study showed 98% clinical resolution at 14 days with no relapse by 28 days using 5 days of therapy. 3

When MRSA Coverage is NOT Needed

Do not routinely add MRSA coverage for typical arm cellulitis without specific risk factors. 1 Beta-lactam treatment succeeds in 96% of patients, confirming that MRSA coverage is usually unnecessary. 1 This represents overtreatment and increases antibiotic resistance without improving outcomes. 1

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when these specific risk factors are present: 1

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Evidence of MRSA infection elsewhere or known nasal MRSA colonization 1
• Systemic inflammatory response syndrome (SIRS) - fever, tachycardia, hypotension 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

MRSA Coverage Options (when indicated):

• Clindamycin 300-450 mg orally every 6 hours - covers both streptococci and MRSA, avoiding need for combination therapy (use only if local MRSA resistance <10%) 1
• Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin - combination provides dual coverage 1
• Doxycycline 100 mg twice daily PLUS cephalexin - alternative combination 1, 4

Critical caveat: Never use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1

Penicillin Allergy Considerations

For patients with penicillin allergy: 1, 2

• Clindamycin 300-450 mg every 6 hours - ideal option covering both streptococci (99.5% of S. pyogenes remain susceptible) and MRSA 2
• Cross-reactivity between penicillins and cephalosporins is only 2-4%, so cephalexin may still be used in non-immediate hypersensitivity reactions 1

Essential Adjunctive Measures

Beyond antibiotics, these interventions hasten improvement: 1

• Elevate the affected arm above heart level to promote gravity drainage of edema and inflammatory substances 1, 2
• Examine for and treat predisposing conditions: tinea pedis, venous insufficiency, lymphedema, eczema 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1

Hospitalization Criteria

Admit patients with any of the following: 1

• SIRS criteria (fever >38°C, tachycardia >90, altered mental status) 1
• Hypotension or hemodynamic instability 1
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing fasciitis (severe pain out of proportion, rapid progression, skin anesthesia, bullous changes) 1
• Failure of outpatient treatment after 24-48 hours 1

Common Pitfalls to Avoid

• Do not extend treatment to 7-14 days based on tradition - 5 days is sufficient if clinical improvement occurs 1
• Do not add MRSA coverage reflexively - reserve for specific high-risk scenarios only 1, 2
• Do not continue ineffective antibiotics beyond 48 hours - progression despite appropriate therapy indicates resistant organisms or deeper infection 1
• Do not use fluoroquinolones (levofloxacin) as first-line - reserve for beta-lactam allergies, as they lack adequate MRSA coverage and promote resistance 1

Monitoring Response

Reassess within 24-48 hours to verify clinical improvement. 1 If no improvement with appropriate first-line antibiotics, consider: 1

• Resistant organisms (add MRSA coverage) 1
• Abscess requiring drainage (obtain ultrasound if uncertain) 1
• Cellulitis mimickers (deep vein thrombosis, contact dermatitis) 1
• Necrotizing infection requiring surgical consultation 1